The objective of the proposed research is to determine how the structure of the lipid-water interface regulates the reaction, cholesterol plus fatty acid reversibly yields cholesteryl ester plus H2O and the cholesterol esterases from pancreas, liver and aorta. To accomplish this, we will determine thermodynamic and kinetic parameters governing the reaction and the enzymes which catalyze it. As a model for interfaces like membranes and the surface of aortic lipid deposits, at which the enzymes normally function, we will use substrate containing monolayers at the air-water interface. With this system we can control surface area and composition and hence, molecular packing density, orientation and phase distribution. The lipid-water interface will also be characterized by physical methods and by combining the data from physical and enzymatic studies we can determine how interfacial structure affects the direction and extent of the cholesterol esterase reaction and rate at which it proceeds. The regulation of this reaction contributes to the overall distribution of free and esterified cholesterol in the body and, in particular, the tissues and enzymes to be studied are important to the progression and regression of atheroscerosis.